Phorbol esters potentiate glucocorticoid-induced cytotoxicity in CEM-C7 human T-leukemia cell line.

Phorbol ester tumor promoter, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is synergistic with dexamethasone to cause growth inhibition of CEM-C7 human T-leukemia cell line. A specific saturable binding component which may mediate the phorbol ester effects has been identified by using [20-(3)H]phorbol 12,13-dibutyrate in a whole cell binding assay. Saturation of the specific binding occurs at a concentration (approx. 100 nM) consistent with causing maximal cytotoxicity. Scatchard analysis of the binding after 15 min at 37 degrees C demonstrates a single class of binding sites. The number is 194,000 sites per cell. Other phorbol esters are also cytotoxic to CEM-C7 cell in the presence of 30 nM dexamethasone in an approximate proportion to their activity in competing for [20-(3)H]phorbol 12,13-dibutyrate binding. Phorbol 12, 13-didecanoate, 4-O-methyl PMA, 4-beta-phorbol do not compete for specific binding. The synergism of phorbol esters and dexamethasone on CEM-C7 cells is reversible by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7). However, by treating CEM-C7 cells with TPA for 48 h there is not any increase in the affinity or levels of glucocorticoid receptor. It is tentatively concluded that phorbol esters may play an important role linked to the glucocorticoid-induced growth inhibition in CEM-C7 human T-leukemic cell.